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The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats. [ABSTRACT FROM AUTHOR]

Background Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase ( FAAH) and monoacyl glycerol lipase ( MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/ MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Methods Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension ( CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. Key Results PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response ( VMR). Conclusions & Inferences The selective FAAH inhibitor and dual FAAH/ MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Taurine is an abundant amino acid that is widely distributed in human and animal tissues. Pharmacodynamic studies show that taurine has hypotensive and myocardial protective effects. Studies in isolated tissue baths show that taurine relaxes precontracted arteries. This study aimed to show the effects of taurine on human internal mammary artery (IMA) in vitro and to explain the mechanisms of its effects. METHODS: The response in the IMA was recorded isometrically by a force displacement transducer in isolated organ baths. Taurine (20, 40, 80 mM) was added to organ baths after precontraction with KCl (45 mM) or serotonin (5-HT, 30 µM). Taurine-induced relaxations were also tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), the nitric oxide synthase inhibitor L-NAME (100 µM), the large conductance Ca2+-activated K+ channel inhibitor tetraethylammonium (TEA, 1 mM), the ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10µM), the voltage-sensitive K channel inhibitor 4-aminopyridine (4-AP, 1 mM) and the inward rectifier K+ channel inhibitor barium chloride (BaCl2, 30 µM). RESULTS: Taurine did not affect the resting tone of IMA. However, it produced relaxation in the 5-HT and KCl-precontracted preparations. The relaxation to IMA was not affected by GLI, 4-AP, BaCl2, indomethacin and L-NAME. But, TEA inhibited taurine-induced relaxations significantly (p < 0.05). CONCLUSIONS: The preincubation of IMA with taurine antagonized KCl and 5-HT induced contractions in a concentration dependent manner, while it did not affect the resting tone. The relaxations to taurine were significantly antagonized by pretreatment with TEA. These results suggest that mechanism of vasodilator effect of taurine in IMA may be the activation of large conductance Ca2+-activated K+ channels. [ABSTRACT FROM AUTHOR]

Background and purpose:The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5-HT receptors (5-HT1–7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5-HT7 receptor. We aimed to examine the role of spinal 5-HT7 receptors in the antinociceptive effects of systemic morphine.Experimental approach:The involvement of spinal 5-HT7 receptor in systemic morphine antinociception was compared to that of the 5-HT1A and 5-HT2 receptors by using the selective 5-HT7 receptor antagonist, SB-269970, the selective 5-HT1A receptor antagonist, WAY 100635, the selective 5-HT2 antagonist ketanserin as well as the non-selective 5-HT1,2,7 receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail-flick test.Key results:I.t. administration of SB-269970 (10 μg) and metergoline (20 μg) completely blocked the s.c. administered morphine-induced (1, 3, 5 and 10 mg kg−1) antinociception in a time-dependent manner. Additionally, i.t. administration of SB-269970 (1, 3, 10 and 20 μg) and metergoline (1, 5, 10 and 20 μg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10 mg kg−1, s.c.). I.t. administration of WAY 100635 (20 μg) or ketanserine (20 μg) did not alter morphine-induced (1, 3, 5 and 10 mg kg−1, s.c.) antinociception.Conclusion and implications:These findings indicate that the involvement of spinal 5-HT7, but not of 5-HT1A or of 5-HT2 receptors in the antinociceptive effects of systemic morphine.British Journal of Pharmacology (2006) 149, 498–505. doi:10.1038/sj.bjp.0706854; published online 14 August 2006 [ABSTRACT FROM AUTHOR]

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels.

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the K + channel inhibitors tetraethylammonium (1 mM), glibenclamide (10 µM) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine-induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl-induced contractions in RA, and suggest that large conductance Ca 2+ -activated K + channels may be involved in taurine-induced relaxation of RA., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Purpose: To evaluate whether or not the bladder function can be protected by supporting the detrusor with decorin levels during the fibrotic process., Methods: Forty-two male rabbits were divided into three main groups, partial bladder outlet obstruction (pBOO) group, pBOO + intradetrusor decorin-injected (IDI) group and control group. Both pBOO and pBOO + IDI groups were divided into three subgroups according to the killing schedule. Histopathological, immunohistochemical and pharmacodynamics studies were performed for the evaluation of fibrotic process and tissue characteristics., Results: Histopathological evaluation revealed statistically significant high fibrosis levels for both pBOO and pBOO + IDI groups when compared with control. Strikingly the antifibrotic effect of decorin was significant on 2nd, 4th and 8th week and increased as time passed. Immunohistochemical analysis was revealed high expressions of anti-TGF-β1 and decorin levels in all pBOO + IDI groups. Pharmacodynamical results were also revealed better contraction responses in favor of 2nd, 4th and 8th week groups of pBOO + IDI groups, when compared with pBOO groups. In addition, the contraction responses against the depolarizer agent KCl were increased in the three decorin-administrated groups., Conclusion: Our study demonstrates the antifibrotic effects of decorin on bladder fibrosis. Strikingly, this antifibrotic effect is shown in histopathological, immunohistochemical and pharmacodynamics studies. Although further studies are warranted to make more decisive inferences regarding its clinical use, our study has the proper pride to be the first step of this time course.

The increase of endocannabinoid tonus by inhibiting fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) represents a promising therapeutic approach in a variety of disease to overcome serious central side effects of exocannabinoids. Recent studies reported that systemic administration of FAAH and MAGL inhibitors produce antipruritic action. Dual FAAH/MAGL inhibitors have also been described to get enhanced endocannabinoid therapeutic effect. In this study, we examined and compared dose-related antipruritic effects of systemic (intraperitoneal; ip) or intrathecal (it) administration of selective FAAH inhibitor PF-3845 (5, 10, and 20 mg/kg, i.p.; 1, 5, and 10 µg, i.t.), MAGL inhibitor JZL184 (4, 20, and 40 mg/kg, i.p.; 1, 5, and 10 µg, i.t.) and dual FAAH/MAGL inhibitor JZL195 (2, 5, and 20 mg/kg, i.p.; 1, 5, and 10 µg, i.t.) on serotonin (5-HT)-induced scratching model. Serotonin (25 μg) was injected intradermally in a volume of 50 μl into the rostral part of skin on the back of male Balb-C mice. Both systemic or intrathecal administration of PF-3845, JZL184 or JZL195 produced similar dose-dependent antipruritic effects. Our results suggest that endocannabinoid-degrading enzymes FAAH and MAGL are involved in pruritic process at spinal level. FAAH, MAGL or dual FAAH/MAGL inhibitors have promising antipruritic effects, at least, in part through spinal site of action.

Objective: To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice., Material and Methods: Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 µl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0-12 min) and the late phase (Phase II: 12-30 min)., Results: LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test., Conclusion: Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain.

Intradermal injection of pruritogens such as serotonin, histamine and compound 48/80 into the skin and then, the evaluation of the scratching behavior is the commonly used animal model to advance pruritic research and drug development. However, predictive validity of this model is poorly documented. There is a close interaction between itch and pain sensations with regard to mediation through an anatomically and functionally identical neuronal pathway. One approach is whether the existing animal model of itch differentiates itch or pain to show efficacy of clinically effective analgesic drugs as a back translation. In this study, we explored the effects of different group of analgesic drugs on serotonin and compound 48/80-induced scratching behavior in Balb-C mice. Serotonin (25 μg) and compound 48/80 (100 μg) was injected intradermally in a volume of 50 μl into the rostral part of skin on the back of male mice and scratches were counted for a 30-min observation period. Morphine (1, 3, 10 mg/kg), tramadol (20, 40, 80 mg/kg), cannabinoid agonist CP 55,940 (0.1, 0.3, 1 mg/kg), paracetamol (100, 200, 300 mg/kg) and diclofenac (50, 100, 200 mg/kg) were given intraperitoneally 30 min prior to pruritogen injection. The analgesic drugs dose dependently blocked serotonin and compound 48/80-induced straching behavior with exerting complete inhibition at certain doses. Our data suggests that intradermal pruritogen-induced scratching models may not discriminate pain and itch sensations and give false positive results when standard analgesic drugs are used.

The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia., (Copyright © 2015. Published by Elsevier B.V.)

Objectives: We researched the survival of bone marrow-derived mesenchymal stem cells (MSCs) and the results of MSCs' injected into decompensated bladders in a rabbit model., Methods: Partial bladder neck obstruction (PBNO) and subsequent decompensation of the bladder was achieved by wrapping the bladder neck with autologous rectus fascia. In the first aspect of the experiment 18 rabbits underwent MSC injection into the decompensated bladder to prove the survivability of injected MSCs. For this purpose MSCs were isolated, transfected with Green Fluorescent Protein (GFP), and injected into the detrusor layer. Once viability was assessed in the first phase, an additional 10 rabbits underwent PBNO in the second phase. Five of these animals underwent subsequent MSC injection (group 3, stem cell) and 5 did not (group 2, obstruction). Both groups were compared to 5 controls (group 1). Urodynamics were performed in all groups. After the animals were sacrificed the groups were compared via morphometric analysis, contractile response to carbachol and KCl, and muscarinic receptor type analysis., Results: On morphometric analysis, collagenous area rates were 43, 53 and 37% in group 1, 2 and 3, respectively. There was no statistically significant difference between groups in terms of bladder weight, bladder capacity and vesical pressure. The contractile effects of KCl and muscarinic agonist carbachol were significantly higher in groups 1 and 3 than group 2. The response to carbachol was antagonized by muscarinic M(1) and M(3) receptor antagonist pirenzepine and abolished by muscarinic M(3) receptor antagonist 4-DAMP in all groups., Conclusions: The injection of MSCs decreased the collagenous area, increased detrusor contractility. Functional M(3) receptors were also expressed in MSCs-injected bladder smooth muscle as well as in control group.

Purpose: To compare sulbactam-ampicillin and cefuroxime antibiotics for prophylaxis of percutaneous nephrolithotomy (PCNL) and to find out the optimal regimen for antibiotic maintenance to prevent systemic inflammatory response syndrome (SIRS)., Patients and Methods: Between February 2010 and March 2011, a total of 198 patients in whom PCNL was performed were prospectively randomized into two main groups regarding the type of prophylactic antibiotic (group1: sulbactam-ampicillin, group 2: cefuroxime). Each group was further randomized according to duration of antibiotic maintenance (a: single dose prophylaxis, b: additional dose 12 hours after prophylaxis, c: beginning with prophylactic dose until the nephrostomy tube removal). Seven patients in whom purulent urine was obtained through the access needle were excluded from the study. Groups were compared in terms of stone- and operation-related factors as well as preoperative urine cultures, access cultures, stone cultures, postoperative urine cultures, and presence of SIRS., Results: A total of 191 patients (group 1: 95, group 2: 96) were evaluated. Mean patient age, body mass index, stone size, and perioperative outcomes were similar. Positive culture rates did not differ between groups. SIRS was observed in 13 (43.3%) patients in group 1 and 17 patients (56.7%) in group 2 (P=0.44). The relation between duration of antibiotic maintenance and SIRS development was not different in each group (P=0.95 for group 1, P: 0.39 for group 2). Urosepsis was observed in two patients, and one patient died because of septic shock., Conclusions: Sulbactam-ampicillin and cefuroxime antibiotics can be used safely for prophylaxis of PCNL. Single dose administration is sufficient.

Cannabinoids produce antinociceptive and antihyperalgesic effects mainly through activation of the inhibitory CB1 receptors. The demonstration that antinociceptive effects of systemic cannabinoids are significantly diminished following surgical dorsolateral funiculus lesion provides evidence that supraspinal sites and descending pain modulatory pathways play crucial roles in systemic cannabinoid analgesia. In this review, we will firstly provide a background, brief overview of descending modulatory pathways followed by descending pathways implicated in cannabinoid analgesia. We will then describe the recent evidence of the involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. This review will provide evidences that systemically administered cannabinoids reinforce the descending serotonergic and noradrenergic pathways to produce acute antinociceptive effects via spinal 5-HT7, 5-HT2A and alpha-2 adrenoceptors activation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although some studies have shown the essential role of descending serotonergic pathways and spinal 5-HT(1A), 5-HT(2A), or 5-HT(3) receptors in the antinociceptive effects of paracetamol, other studies have presented conflicting results, and the particular subtype of spinal 5-HT receptors involved in paracetamol-induced analgesia remains to be clarified. Recent studies have demonstrated the importance of spinal 5-HT(7) receptors in descending serotonergic pain inhibitory pathways. In this study, we investigated the role of descending serotonergic pathways and spinal 5-HT(7) receptors compared with 5-HT(3) and 5-HT(2A) receptors in the antinociceptive and antihyperalgesic effects of paracetamol. Tail-flick, hot plate and plantar incision tests were used to determine nociception in male BALB/c mice. Lesion of serotonergic bulbospinal pathways was performed by intrathecal (i.th.) injection of 5,7-dihydroxytryptamine (5,7-DHT), and spinal 5-HT levels were measured by HPLC. To evaluate the particular subtypes of the spinal 5-HT receptors, the selective 5-HT(7), 5-HT(3) and 5-HT(2A) receptor antagonists SB 269970, ondansetron and ketanserin, respectively, were given i.th. after oral administration of paracetamol. Oral paracetamol (200, 400 and 600 mg/kg) elicits dose-dependent antinociceptive and antihyperalgesic effects. I.th. pretreatment with 5,7-DHT (50 μg) sharply reduced 5-HT levels in the spinal cord. Depletion of spinal 5-HT totally abolished the antinociceptive and antihyperalgesic effects of paracetamol. I.th. injection of SB 2669970 (10 μg) blocked the antinociceptive and antihyperalgesic effects of paracetamol, but ondansetron and ketanserin (10 μg) did not. Our findings suggest that systemic administration of paracetamol may activate descending serotonergic pathways and spinal 5-HT(7) receptors to produce a central antinociceptive and antihyperalgesic effects., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples., Materials and Methods: We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients., Results: System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes., Conclusion: This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

Aims: To examine whether obstruction changes the expression of prostaglandins (PGs) in bladder, intravesical low-dose aspirin could be used as a new route of drug administration, this way of administration influences PGs' expression, and contractile function of the bladder is protected after treatment., Methods: Eighteen rabbits were divided into three groups. Sham-operated group (group 1) included 6 rabbits. Twelve rabbits were partially obstructed for 70 days. Six of these 12 rabbits not receiving any treatment constituted obstructed group (group 2). The remaining six rabbits received 2  mg/kg/day aspirin (group 3). One rabbit in each group was evaluated on 1st, 7th, 14th, 28th, 42nd, and 70th days following obstructive surgery. After scarification, the percentage of collagenous area and concentrations of PGE2 and PGF2-alpha were measured. Contractile responses to field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined., Results: Wet tissue PGE2 and PGF2-alpha levels were higher in obstructed group than the other groups. Aspirin decreased the percentage of collagenous area in group 3 compared to the group 2, but this difference was not statistically significant. The strips from aspirin groups resulted in better contractile response to cholinergic stimulation with KCl, but this difference was not statistically significant between the obstructed and aspirin groups. Similarly, carbachol did not elicit significantly greater concentration-dependent contraction in strips from obstructed group compared to those from aspirin groups. Maximum responses to EFS were not significant in aspirin group compared to those from obstructed group., Conclusions: Intravesical aspirin may have protective effect on partially obstructed bladder., (Copyright © 2011 Wiley Periodicals, Inc.)

Background and Purpose: Operative time is an important perioperative factor and is related to postoperative complications and procedural cost-effectiveness. There are few studies, however, investigating factors that affect operative time during percutaneous nephrolithotomy (PCNL). In this study, patient and kidney stone-related factors that influence operative time were analyzed., Materials and Methods: Clinical records from 1897 patients with renal calculi who underwent PCNL were retrospectively reviewed, and these patients were divided into two groups based on their median operative time (group 1: ≤60 min; group 2: >60 min). Multivariate analyses as well as univariate analyses including chi-square, Fisher exact and Mann Whitney U tests were used to investigate the effects of independent variables on operative time, including patient and kidney stone-related factors such as age, sex, body mass index, history of ipsilateral open surgery, shockwave lithotripsy, presence of hydronephrosis, stone burden, stone type and opacity, and surgical experience., Results: The mean operative time was 64.9±27.6 minutes (range 10-220 min). Univariate analyses determined that a history of open surgery, presence of hydronephrosis, stone type and size, and surgical experience correlated with operative time (P<0.05 for all). Multivariate analyses revealed that presence of hydronephrosis (odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.17-1.78, P=0.002), stone type (OR: 2.12, 95% CI: 1.69-2.70, P<0.0001), stone burden (OR: 2.44, 95% CI: 1.85-3.12, P<0.0001), and surgical experience (OR: 0.56, 95% CI: 0.46-0.70, P<0.0001) were significant independent factors in influencing operative time., Conclusions: Presence of hydronephrosis, renal stone size and type significantly affect the operative time during PCNL. The duration of the operation was also observed to decrease with increased surgical experience.

Objectives: To investigate the relation of testosterone-induced relaxation with smooth muscle K+ channels in human internal spermatic veins. Testosterone induces relaxation in human isolated internal spermatic veins, and this effect decreases in high-grade varicocele (recently reported)., Methods: The responses of isolated internal spermatic veins from patients with varicocele were recorded isometrically using a force displacement transducer. After contracting the venous rings with 45 mM KCl, relaxation with testosterone (0.1-300 μM) was recorded in the absence or presence of large conductance calcium-activated K+ channel and the voltage-sensitive K+ channel inhibitor tetraethylammonium, adenosine triphosphate-sensitive K+ channel inhibitor glibenclamide, voltage-dependent inward rectifier K+ channel inhibitor barium chloride, and voltage-sensitive K+ channel inhibitor 4-aminopyridine., Results: Testosterone induced relaxation in human isolated internal spermatic veins in the absence of inhibitors (maximal effect 52.88±6.72, n=24). Although tetraethylammonium, barium chloride, and 4-aminopyridine did not alter the testosterone-induced relaxant responses, GLI inhibited these responses., Conclusions: These results have demonstrated that testosterone induces relaxation in human isolated internal spermatic veins of patients with varicocele by way of adenosine triphosphate-sensitive K+ channels., (Copyright © 2011 Elsevier Inc. All rights reserved.)